People under 65 may lower dementia risk with improved diet, lifestyle, other factors

 

• Young-onset dementia, also known as early-onset dementia, occurs when a person younger than 65 develops dementia.
• Researchers based in England and the Netherlands collaborated on a cohort study about young-onset dementia and focused on risk factors that could contribute to developing the disease.
• The scientists learned that 15 risk factors contribute to developing young-onset dementia, including diabetes, alcohol abuse disorder, and social isolation.

According to the Centers for Disease Control and Prevention (CDC), nearly 6 million adultsTrusted Source age 65 and older have Alzheimer’s disease (AD), the most common form of dementia, which is about 1 out of every 10 adults in this age bracket.

Many scientists prioritize dementia research, which includes finding medications to slow disease progression and learning more about changes people can make to reduce symptoms.

Researchers from the University of Exeter in England and Maastricht University in the Netherlands worked together to study young-onset dementia.

They focused their research on identifying risk factors for young-onset dementia and whether targeting these risk factors could reduce the risk of developing early dementia.

The research was recently published in JAMA NeurologyTrusted Source.

How common is early onset dementia?

Alzheimer’s Disease International projects dementia cases to increase from 55 million people worldwide in 2020 to 139 million people by 2050.

With such a staggering estimate, finding ways to identify factors that contribute to developing the disease is of utmost importance.

While young-onset dementia is rare, the CDC reportsTrusted Source that young-onset Alzheimer’s disease still affects around 200,000 people in the United States.

The researchers say that since most of the research into young-onset dementia focuses on genetics, they wanted to look more into how modifiable risk factors affect this form of dementia. Some modifiable risk factors include smoking, mental health, and alcohol intake.

The researchers used data from the U.K. Biobank for the study; the U.K. Biobank has nearly a half million participants who provide their genetic and other medical data. The purpose of the U.K. Biobank is to study health issues and make improvements in public health.

The scientists in the current project used data from nearly 356,000 participants who met the inclusion guidelines of being under age 65 and not having any form of dementia. Women comprised just over half (55.3%) of the participant pool.

The participants for U.K. Biobank underwent their initial assessments between 2006 and 2010 and followed up over the years, with the last follow-up in March of 2021.

Some information collected from the participants includes:

• biological samples
• socioeconomic status
• education
• alcohol or drug use
• psychiatric data
• environmental exposure to toxins
• general health information

After gathering information about the participants, the researchers analyzed the data to see whether there was an uptick in the incidence of young-onset dementia in people exposed to certain risk factors.

New risk factors linked to early-onset dementia

Throughout the follow-up period, 485 people developed young-onset dementia.

The researchers identified 39 risk factors, and after careful analysis, determined that 15 of these risk factors increased the risk of young-onset dementia.

Some of the newly-identified risk factors include:

• lower level of education
• alcohol use disorder
• social isolation
• vitamin D deficiency
• high C-reactive protein level
• depression
• stroke
• diabetes

“While further exploration of these risk factors is necessary to identify potential underlying mechanisms, addressing these modifiable factors may prove effective in mitigating the risk of developing [young onset dementia] and can be readily integrated in current dementia prevention initiatives,” the authors wrote.

The study findings show that staying on top of both mental and physical health is important, especially during mid-life.

Further, many risk factors are things people can take action on, such as expanding their social activities or asking their healthcare team to assess their vitamin D levels.

Early intervention key to preventing dementia, Alzheimer’s

Dr. David Merrill, a geriatric psychiatrist and director of the Pacific Neuroscience Institute’s Pacific Brain Health Center in Santa Monica, CA, spoke about the study with Medical News Today. Dr. Merrill weighed in on some of the risk factors the researchers identified.

When asked why depression could contribute to an increased risk for developing young-onset dementia, Dr. Merrill explained that “depression has both direct and indirect effects on brain structure and function.”

“We know that chronic depression can lead to more rapid loss of brain volume over time with aging,” Dr. Merrill noted. “Depression also tends to decrease levels of social and cognitive activities, which are themselves risks for cognitive decline.”

“Untreated depression can lead to progressively worsening cognitive decline, decline that may lessen or even stop if the depression is addressed,” he added.

Dr. Merrill touched on education level as a risk factor as well.

“[Socioeconomic status] and education level are developmental factors related to ‘cognitive reserve.’ Cognitive reserve can be thought of as the buffer against developing symptomatic dementia,” he said.

Dr. Allison B. Reiss, associate professor of medicine at NYU Long Island School of Medicine and part of the Alzheimer’s Foundation of America, also commented on the study to MNT:

“There are many things that can contribute to dementia that are in our environment and they are now more and more recognized,” noted Dr. Reiss. “The brain needs a very stable environment to function well and that includes many factors that are within our control or can be treated very well if the person receives good healthcare. The finding that genetics are not destiny is a hopeful one and indicates that we can take action to keep our brains at peak function starting in the younger years,” commented Dr. Reiss.

Dr. Reiss said that it is helpful for people to know there are things they can do to improve their chances of avoiding young-onset dementia.

“Diet, lifestyle, stress reduction, heart-healthy behaviors and seeking help for depression can make a difference,” pointed out Dr. Reiss.

“Improving financial status and making sure that people have enough to eat, safe housing and social connections does matter. It is important to see your healthcare provider regularly, follow recommended screening guidelines and work with that person or team to maintain overall good health.”

Source - Medical News Today        

Stress response linked to brain cell death in early-onset dementia

 

• A new study challenges the concept that protein aggregates in the brain are the direct cause of cell death in neurodegenerative diseases.
• The researchers noted the culprit is the body’s inability to turn off the stress response in brain cells.
• The findings highlight the potential for using certain drugs to deactivate the brain’s stress response and maintain the activity of a newly identified protein complex, SIFI.
• The new insights shift the focus from targeting protein aggregates to managing the stress response mechanism and introduce the potential for new treatment strategies.

Many neurodegenerative conditions, including Alzheimer’s disease (AD) and Parkinson’s disease (PD), have been linked to the buildup of protein aggregates in the brain, leading researchers to believe that these protein clumps are responsible for the death of brain cells.

As a result, efforts to find treatments focused on dissolving and eliminating these protein formations have largely been unsuccessful.

But now, new research published in NatureTrusted Source challenges this assumption.

The study authors propose the lethal factor for brain cells is not the protein aggregates themselves but the inability of the body to deactivate the stress response in these cells and maintain the activity of a newly identified protein complex known as SIFI.

Their study demonstrates that administering a drug that can halt this stress response can rescue cells affected by a neurodegenerative condition known as early-onset dementia.

Lead researcher Michael Rapé, PhD, professor and head of the Division of Molecular Therapeutics, Dr. K. Peter Hirth Chair of Cancer Biology at UC Berkeley, said this discovery opens up potential new ways to treat neurodegenerative diseases. He explained that we find clumps of proteins, known as aggregates, inside cells in certain diseases.

Prof. Rapé told Medical News Today the new research highlights how “a set of neurodegenerative diseases are connected through their persistent activation of a stress response pathway (the cellular stress response to mitochondrial import defects).”

“The stress response is normally turned off by a dedicated factor — the first example of ‘stress response silencing’ — and mutations in this factor cause early-onset dementia.”

— Prof. Michael Rapé, lead study author.

 How protein aggregates affect the stress response

Normally, cells can turn off their stress response after it’s no longer needed “by diverting the silencing factor (SIFI) from its stress response targets,” Prof. Rapé said.

However, in these diseases, the aggregates prevent the protein complex SIFI from doing its job, which means the cell’s stress response stays active when it shouldn’t.

The research has shown that we can help cells affected by these aggregates, such as those seen in early onset dementia, by using drugs to restore the normal process of turning off the stress response.

These treatments work even without removing the aggregates.

This finding is crucial because it suggests that the real danger from these aggregates is not the aggregates themselves but how they keep the stress response running.

Keeping the stress response constantly active can harm the cells, which might be a key factor in how these diseases progress.

Dr. David Merrill, PhD, board certified adult and geriatric psychiatrist and director of the Pacific Neuroscience Institute’s Pacific Brain Health Center in Santa Monica, CA, not involved in this research, told MNT that this research “represents a promising new way to treat otherwise incurable neurodegenerative diseases.”

“Turning off the stress response in cells that have otherwise lost that capability is a worthwhile approach to study,” Dr. Merrill explained.

Activated stress response leads to cell death

Diseases that might benefit from this finding include genetic conditions leading to ataxia, which is characterized by a loss of muscle control, as well as early-onset dementia.

The research also highlights that other neurodegenerative disorders, such as Mohr-Tranebjærg syndrome, childhood ataxia, and Leigh syndrome, exhibit similar overactive stress responses and share symptoms with the early-onset dementia studied.

The research team had previously believed that protein aggregates were directly lethal to neurons, perhaps by damaging internal cell structures.

However, their new insights reveal that these aggregates actually block the shutdown of a stress response that cells initially activate to manage malfunctioning proteins.

The perpetual activation of this stress response is what leads to cell death.

The team suggests that this mechanism could also be relevant to more prevalent diseases that feature widespread protein aggregation, like Alzheimer’s disease and frontotemporal dementia, although further research is necessary to explore the impact of stress signaling in these conditions.

Silencing the stress response

New treatment strategies could eventually involve “compounds that turn off the stress response kinase (HRI),” Prof. Rapé explained.

However, the “best way to treat neurodegenerative disease would be to limit aggregation and silence stress response signaling at the same time, reminiscent of combination therapy now in use in oncology,” the study author added.

Further research is needed, explained Dr. Merrill. “We need robust funding and rapid development of clinical trials targeting mechanisms like the one discovered in this work,” he noted.

“There is still much work to be done, but stress response silencing may prove to be a valuable way to slow or stop [the] progression of some neurodegenerative diseases,” Dr. Merrill concluded.

Source - Medical News Today

Scientists find new protein linked to early-onset dementia

 

• Scientists at the Medical Research Council (MRC) Laboratory of Molecular Biology in Cambridge, UK, have identified a novel protein called TAF15 forming aggregated structures in cases of frontotemporal dementia, challenging previous assumptions about the condition.
• This discovery is a novel addition to the limited set of proteins recognized for aggregating in neurodegenerative disorders like Alzheimer’s.
• This finding not only paves the way for advanced diagnostic tools and treatments but also raises the intriguing possibility that TAF15 may be linked to both frontotemporal dementia and motor neuron disease, shedding new light on these debilitating disorders.

Most neurodegenerative disorders, such as dementia, involve proteins clustering into filaments known as amyloids.

Novel protein may contribute to frontotemporal dementia

Frontotemporal dementia arises from the deterioration of the brain’s frontal and temporal lobes, which oversee emotions, personality, behavior, language comprehension and speech.

This condition typically manifests at an earlier age compared to Alzheimer’s disease, frequently being diagnosed in individuals between 45 and 65 years old. However, it can also present in individuals both younger and older.

In their new research, a team of scientists uncovered aggregated protein structures that may serve as a focal point for potential advancements in diagnostic assessments and therapies.

With the identification of the key protein and its structure, the researchers are now poised to focus on it to diagnose and treat this specific form of frontotemporal dementia.

This approach mirrors the strategies already in progress for targeting amyloid-beta and tau protein aggregates—hallmark features of Alzheimer’s disease.

Utilizing advanced cryo-electron microscopy to examine the brain

The scientists utilized advanced cryo-electron microscopy (cryo-EM) techniques to examine protein aggregates at an atomic level resolution in the brains of four individuals with this form of frontotemporal dementia.

Until now, scientists had assumed that a protein named FUS was responsible for aggregation in this type of dementia, drawing parallels with other neurodegenerative disorders.

Utilizing cryo-electron microscopy (cryo-EM), the MRC Laboratory of Molecular Biology scientists successfully determined that the protein aggregates found in each brain shared an identical atomic structure.

Surprisingly, the responsible protein was not FUS but another protein called TAF15.

The researchers clarified that this outcome was unexpected, as prior to this study, TAF15 had not been recognized for its role in forming amyloid filaments in neurodegenerative conditions, and no information about its structural characteristics existed.

Cryo-EM is revolutionizing our comprehension of the molecular mechanisms underlying dementia and neurodegenerative diseases in a broader context by providing insights that were previously unattainable with earlier technologies.

The researchers acknowledged that the intricate nature of conducting cryo-electron microscopy limited their examination to only four individuals’ brains.

Nevertheless, with our newfound knowledge of the pivotal protein and its structure, there is the prospect of creating tools for screening hundreds of patient samples to assess the extent of these abnormal protein aggregates.

In most cases, scientists have pinpointed the proteins responsible for this aggregation, enabling them to focus on these proteins for diagnostic assessments and therapies.

However, in approximately 10% of frontotemporal dementia cases, researchers had not yet determined the specific protein responsible.

Now, researchers have successfully identified the aggregated structures of the TAF15 protein in these particular cases.

The findings were published in NatureTrusted Source.

Frontotemporal dementia and motor neuron disease

Some individuals affected by frontotemporal dementia also experience motor neuron disease, a condition characterized by a progressive loss of muscle control.

In this investigation, two individuals who had both conditions donated their brains for study.

In these cases, the researchers detected the same aggregated form of the TAF15 protein in brain regions associated with motor neuron disease.

The presence of identical TAF15 aggregates in two individuals who had both frontotemporal dementia and signs of motor neuron disease raises the possibility that TAF15 may contribute to the development of both disorders.

Further research needed to investigate the impact of TAF15

The research team is currently examining whether these abnormal TAF15 aggregates are present in individuals with motor neuron disease who do not exhibit symptoms of frontotemporal dementia.

James Giordano, PhD, MPhil, Pellegrino Center Professor of Neurology and Biochemistry at Georgetown University Medical Center, not involved in this research, told Medical News Today that “this study further examined the possibility that additional abnormal proteins may be contributory to the neuropathological process of fronto temporal lobar degeneration and dementia (FTLD).”

“The study was well conducted and utilized a fairly broad sample of brain tissue taken from affected patients to evaluate the presence and extent of TAF protein, a variant abnormal protein constituent, which, together with other known abnormal proteins (such as characteristic tau and alpha-synuclein entities), are found in and contributory to the neurodegenerative processes of FTLD.”
— Dr. James Giordano

Dr. Giordano noted that “this study importantly, demonstrated that TAF protein is also present, albeit in somewhat lesser concentration, in the total proteinopathic constituency of the brains of these patients.”

Dr. Giordano noted that the study findings “further support and advance aspects of the amyloid hypothesis of neurodegenerative dementia.”

“Further, the identification of TAF variant may serve as an important diagnostic marker, as well as a potential therapeutic target in the treatment of FTLD,” he explained.

Jennifer Bramen, Ph.D., senior research scientist at the Pacific Neuroscience Institute in Santa Monica, CA, also not involved in this research,“frontotemporal lobe dementia (FTD) is an emotionally challenging disease with no cure.”

Dr. Bramen concluded that “FTD is a heterogenous disease, making it more challenging to research. A better understanding of different subtypes could ultimately lead to more treatment options for patients.”

Source - Medical News Today

In Conversation: New directions in dementia research

 Millions of people around the world live with a form of dementia, which severely affects both their own and their carers’ quality of life. The specific causes behind dementia remain unclear, but researchers are making steady progress in finding out more about its mechanisms. This instalment of In Conversation looks at some of the realities of dementia, and presents new directions in dementia research.

Dementia is a neurocognitive syndrome that refers to a collection of symptoms related to memory loss and the decline of cognitive function.

The most common form of dementia is Alzheimer’s disease, which affects millions of people worldwide. According to data from the Centers for Disease Control and Prevention (CDC), in the United States alone, in 2020, as many as 5.8 millionTrusted Source people had Alzheimer’s disease.

Research conducted by the Alzheimer’s Society in 2019 indicates that over 850,000 people were living with dementia in the United Kingdom that year, and globally, more than 55 millionTrusted Source people live with dementia, according to the World Health Organization (WHO).

There are some treatments that can help alleviate some dementia symptoms, but most forms of dementia are currently incurable, and researchers continue to investigate the mechanisms through which this syndrome develops with a view to developing better treatments and prevention strategies.

In our latest instalment of In Conversation, we spoke with Paula Field, who is a caregiver for her mother who lives with Alzheimer’s disease, and with Dr. Kamar Ameen-Ali, who is a lecturer in biomedical science at Teesside University in the United Kingdom, and who specializes in neurodegenerative diseases, including Alzheimer’s.

This article provides an edited and shortened record of this instalment of our podcast. We have added reference links to key research findings mentioned in it. Please listen to the podcast — below or on your preferred platform — for the full discussion.

Dementia: Definition and genetic risk

Dr. Hilary Guite: Let’s start with an overview of dementia and its causes.

Dr. Kamar Ameen-Ali: I always think that it’s good when we are discussing dementia to start off with a definition of what we mean by it. Often you might hear people use it interchangeably with things like Alzheimer’s disease, but they’re very distinct things.

Dementia, we kind of describe it as an umbrella term. It describes a set of symptoms, it’s a clinical syndrome — those symptoms are often associated with memory impairment. But for a diagnosis of dementia, you also have to have an impairment in one or more other cognitive domains as well — this might be personality, it might be visual-spatial skills, for example.

And as I mentioned, dementia as a clinical syndrome is distinct from something like Alzheimer’s disease, which is a type of brain disease that leads to dementia.

Dr. Guite: Is dementia hereditary?

Dr. Ameen Ali: It depends on what brain disease we’re talking about. So if we’re going to talk about Alzheimer’s disease — which I think is a good idea, because it’s the most common brain disease that leads to dementia — there are some types of Alzheimer’s disease that are hereditary and some types that aren’t.

The most common type of Alzheimer’s disease is what we call sporadic Alzheimer’s disease, and that counts for 97% of Alzheimer’s disease cases. So 3% of cases of Alzheimer’s disease will have that known genetic origin, and this is caused by genetic mutations.

So only a small percentage of actual Alzheimer’s disease cases have got that genetic, known hereditary link.

The real-life impact

Dr. Guite: Thank you. So Paula, you’ve been looking after your mother with dementia alongside working. Can you tell us what you first noticed?

Paula Field: Yes, I am. I think my sister and I first noticed that there were some issues with her memory after my father had died. I think that she had started to develop some form of dementia before that, but [our parents] sort of helped each other out. And I think [our father] helped her through a lot of those daily things.

After he died, I think it became much more obvious [that something was wrong], but, you know, at that stage, we weren’t sure whether [her symptoms were] sort of a grief thing. But it gradually progressed. And it probably took us about 6 months or so after he died to realize that, you know, we probably did need to take her to the doctor, and to find out what was happening.

Dr. Maria Cohut: Paula, how did this affect you and your sister financially and during day to day life?

Paula: Well, I think in the early days, you could have a conversation [with our mother]. [My sister and I] were both working full-time, we’d go visit weekends, so we were there really regularly. In terms of financial impact, at that stage, there wasn’t very much, we just carried on as usual. We didn’t have any [additional] carers or anybody at that stage, we used to just go in as often as we could.

Then, once it got to the point when we had to take her to the doctors for her first memory test, and once the results came back, that’s when we had to start thinking about [arranging] more care. And that’s resulted in my sister having to take a day off a week from her work and spend two afternoons a week with my mom.

She has been doing that for nearly 4 years now. And we have other carers going in about twice a day now want to make sure that she gets up, and give her some lunch and the other one in the evenings, to give her some dinner. They do that about 4 days a week, and we pick up the rest.

How doctors diagnose dementias

Dr. Guite: What sorts of scans and diagnostic process happens nowadays?

Dr. Ameen-Ali: There are different types of scans that can be done, [such as] PET scans and MRI scans.

In terms of how well they can contribute to the diagnosis of brain diseases? Questionable, I think, because if we’re looking for brain changes that are associated with Alzheimer’s disease, for example, the question is how well can we see that pathology in the brain in life. Something like Alzheimer’s disease can actually only be diagnosed post mortem, when we can confirm that those pathological changes in the brain are actually there.

But something like a PET scan or a CT or an MRI scan, they can see whether there is that general atrophy in the brain, and that is something that we would expect to see in something like Alzheimer’s disease, particularly atrophy around the hippocampus, which is the part of the brain that is responsible for different memory processes.

So to a certain degree, these brain scans can help with the diagnosis of a certain brain disease that is leading to dementia, but we have to remember that it can only ever be confirmed post mortem.

Dr. Guite: You mentioned there atrophy, what does that mean?

Dr. Ameen-Ali: Atrophy is basically where the brain tissue degrades. If you were to see a brain that had atrophy, you’d see essentially shrinkage of certain areas of the brain.

Dr. Guite: My understanding is that the new PET scans can look at how the brain metabolizes nutrients, like sugar, and that they can show whether or not there are are some some proteins that get misfolded. Can you just explain what those proteins are — amyloid and tau — and how important they are?

Dr. Ameen-Ali: Amyloid and tau are the kind of characteristic pathological features of Alzheimer’s disease. Amyloid is a protein that will aggregate and clump together in the brain and form plaques, and that’s what we see in Alzheimer’s disease.

These plaques then disrupt neuronal cell function, and then that leads to a lot of those cognitive issues that we talked about earlier.

There’s also tau, which is [another] protein in the brain. Again, it’s another characteristic pathological feature of Alzheimer’s disease. Normally, it’s a protein within axons of nerve cells, and it helps to form what we call microtubules that are responsible for transporting nutrients within the cells.

What we see in Alzheimer’s disease, is that it aggregates into these tangles, and it disrupts cell function in that way, and it affects how cells communicate with one another.

Changes in personality and behavior

Dr. Guite: Paula, after that initial phase and the the memory loss, what else did you start to notice [in your mother]?

Paula: Well, we noticed that she became quite isolated. She didn’t leave the house, she did start to leave her peas on the cooker. And I think, you know, that was the point where we started to go, “Eek, this is getting quite serious.”

She still has some sort of instinctual habit, so she’ll still switch off the switches at the end of the day. That’s something that she’s done forever. But pretty much everything else…

She knows there’s a fridge in her house, and she knows that there should be something on the shelves, and she will put stuff in the fridge. It could be a packet of crisps or it could be a cup. She has this sort of visual memory of the fridge, she sort of knows what it’s for, but she doesn’t quite know how to use it.

But that’s about it. She doesn’t feed herself. If she won’t drink water, she certainly couldn’t take medicines. She does not wash [on her own]. If we ask her to wash her face or something, she’s quite canny, she’ll go in the bathroom, close the door, won’t let you in, and then come out again.

She still believes that she cooks her own dinner, she still believes that she can do all the things that she’s always done. I don’t think it’s denial, necessarily. I think she just [thinks that] it’s happened, therefore, she must have done it.

She has no idea who myself and my sister are — she recognizes us [as familiar faces], but she doesn’t know who we are. She has no knowledge of people going in every day to help her.

She’s not very active, she pretty much sits on her chair everyday with the TV on and looks into space.

Risk factors and what happens in the brain

Dr. Guite: Kam, can I come back to you from that devastating description of change in personality change in behavior, what’s actually happening in the brain? Because earlier you said [changes] started in the hippocampus, which is the area related to managing memories. But it sounds like more things are happening. What what would actually be happening as the dementia progresses?

Dr. Ameen-Ali: This is one of the complexities of these types of brain diseases that lead to dementia: First of all, how they can affect people very differently based upon the parts of the brain that are affected by the disease.

With something like Alzheimer’s disease, we we know that the pathology progresses into certain areas. And as the disease progresses, it starts to affect more areas of the brain, which is why you might initially see some memory problems.

But a lot of people might dismiss them as just getting older until then the disease progresses, and more and more cognitive domains start to be affected. So as the disease progresses to more of the cortical areas, you might see more issues around language around personality, and then visual-spatial issues that you might see later on as the disease progresses into those cortical areas.

Dr. Guite: Can we just look back to and understand why these things are happening? What are the risk factors related to chronic disease and exposures?

Dr. Ameen-Ali: If you remember, earlier on I mentioned sporadic Alzheimer’s disease — the Alzheimer’s disease that occurs in most cases. And it’s usually over the age of 65 that we would see that, so that when we’re talking about risk factors, they’re associated with that type of Alzheimer’s disease.

We have what we call non-modifiable risk factors. Those are those risk genes that I mentioned earlier on. Age and sex are also non-modifiable risk factors. Age is actually the biggest risk factor for something like Alzheimer’s disease.

But we also have these 12 modifiable risk factors. These are things that we do in our life that potentially we could change that can reduce our risk of dementia. And there are also, generally, things that we can do to promote good brain health, generally.

These modifiable risk factors include things like obesity, hypertension, diabetes, smoking, physical inactivity, loneliness… Brain injury is a big one as well.

Dr. Cohut: So some of the risk factors, but also the preventive interventions that get a lot of press are education and social activity. Presumably, the the longer you stay in education, and the more socially active and involved that you are the lower the risk of dementia. What about your mom, Paula? What was her experience of education and also social life?

Paula: Education minimal, if at all. You have to remember, she was born in the early ’30s. Her social social life was pretty good. [My parents] did have a group of friends when they were into their 50s–early 60s. They’d go on holidays together and and stuff like that. But that was quite sporadic.

And then they might see their friends every now and then. But predominantly, I would say they sort of stuck together. My dad was the social one, he had a much more active life.

Dr. Guite: How old was your mom when she left school?

Paula: Certainly no more than about 13. She wasn’t there very often. You’ve got to remember the [impact of the] war and evacuation and all that sort of stuff.

Dr. Guite: What is happening when we’ve got these elements of education, hearing impairment, social contact — how are they protecting against or reducing the incidence of dementia?

Dr. Ameen-Ali: These risk factors that we’ve talked about, we know that they’re associated with an increased risk of dementia. But what we’re trying to work out as scientists and as researchers is: What actually is the mechanism that is linking these risk factors with the kind of the disease that we see that then leads to dementia?

Because we can do studies where we can find out whether there is a significant correlation between these factors and dementia, but what exactly is causing something like brain injury to increase somebody’s risk significantly to then develop dementia?

The way that I like to imagine it is that our research into trying to understand these mechanisms is like the black box, that we’re trying to work out what’s happening inside that black box. So we’ve got these risk factors on one side, which is the input, and then the disease and the pathology, which is the output, but what is happening on the inside?

It’s almost like you’ve got risk factors and protective factors. And, you know, it’s all about that balance between minimizing your risk factors and maximizing the protective factors.

And it’s a game of probability, really, because there’s no guarantee that doing any of these things, you will get dementia. And there’s no guarantee that if you don’t do any of the things that you’ll be protected from it, but it’s all about managing risk, essentially.

Does neuroinflammation play a role?

Dr. Guite: I read that all of those 12 risk factors only account for 40% of dementia cases. So you’ve got the other 60%, which is in your black box. Can I come back to your black box now? Because we’ve got amyloid and tau, and we’ve got these risk factors, but what else is going on?

Dr. Ameen-Ali: Neuroinflammation is quite a significant area of research in terms of looking at a potential mechanism that would be driving brain diseases that lead to dementia.

Neuroinflammation is something that I’m interested in. There is a type of immune cell in the brain called microglia, and they’re involved in an inflammatory response in the brain.

A lot of the research that I’ve done is around brain injury. So I’ve looked at these cells, these microglial cells, and both the acute inflammatory response and also a chronic inflammatory response as a result of brain injury, and how that might be the mechanism that is increasing the risk of dementia after brain injury.

So it’s all about how the cells respond as part of a neuroinflammatory response in the brain. And how, over time, if there is a chronic response, because we know that neuroinflammatory responses are originally designed to be protective, but if it’s if the cells are activated long term, as in chronic activation, could they actually be causing damage? And could that be what is then leading to the development of the pathology that we see in something like Alzheimer’s?

Dr. Cohut: I was also thinking about some recent research that’s been looking at the gut-brain axis, so the link between the bacteria in our gut and what goes on in our brain. And there’s been some talk about the influence of gut bacteria on the brain in the context of dementia. So I’m wondering if that might have anything to do with neuroinflammation at any level?

Dr. Ameen-Ali: It’s possible, because when we’re talking about neuroinflammation, this could be systemic inflammation. It could be inflammation that’s happened at some point in a person’s life. It could be inflammation that has happened and then affected the brain.

So there is the possibility of inflammation that’s happened somewhere else in the blood, in the body that has then led to an inflammatory response in the brain. It doesn’t necessarily have to be from an injury that I look at in the brain, it can be systemic inflammation as well.

Early diagnosis is crucial

Dr. Guite: How are you feeling about the future for dementia and Alzheimer’s?

Paula: It’s a tricky one. I think, in our situation, if we’re to be brutally honest, it’s too late for any sort of treatment for my mom. For us, it’s just about keeping her safe, making sure she’s fed, making sure she drinks…

You know, my question is at what point do you think that people should approach their doctor for a diagnosis or a brain scan? Because, you know, in her case, we didn’t notice it, it was too late. I’m not saying they could have stopped it.

But at what point do you think that we need to get on top of this, and actually not wait until the diagnosis? Because once you’ve got a diagnosis, you know, there’s pretty little that you can do, and it’s sad, it’s a waiting game, and we don’t know what to expect. We had no warning, there was nothing that we could do about it in advance.

Dr. Ameen-Ali: I would say that [obtaining a] diagnosis as early as possible is the best thing to do, really. And that can be really challenging, because often, those early signs can be just dismissed as getting older or not really significant enough.

[However,] the earlier the diagnosis, the better, because [then] treatments will be the most effective. They can’t stop the disease, but they can have a much more significant impact on symptoms the earlier that they’re delivered.

I do think that going forward, we need to be able to diagnose much earlier, if we want to have effective treatments. And in terms of developing treatments, it’s unlikely that we’re going to have one single drug that is going to have a significant impact. Because there’s lots of these different potential disease mechanisms, it’s likely that we’re going to need different drugs that administered together, in parallel that will have any significant effect on disease progression.

Paula: Do you think that, potentially, we could get to a place where testing for or diagnosing dementia will be something like you’d have for breast cancer screening that becomes a routine part of your everyday medical self-care?

Dr. Ameen-Ali: I think so. I think if we have better cognitive tests that are more sensitive to certain types of memory decline, because different types of memory decline at different rates.

If we have sensitive tests, then we can certainly administer them at a certain age when your risk increases. And then hopefully that will start picking people up at an earlier rate when the disease is in its earliest stages. And that’s what I think will have a significant effect on on dementia in the future.

To discover more evidence-based information and resources for Alzheimer’s & dementia, visit our dedicated hub.

Source - Medical News Today